Accounting for nearly one quarter of total deaths in the United States, cancer remains the second leading cause of death behind heart disease. Traditional chemotherapy uses highly potent cytotoxic agents to interfere with the processes of cell proliferation, relying on the premise that rapidly proliferating tumor cells are more likely to be killed than normal cells. This lack of tumor-specificity continues to be a serious issue in cancer treatment, causing undesirable and dose-limiting side effects. Therefore, concentrated efforts have been directed toward the development of tumor-targeted drug delivery systems (TTDDSs), which consist of a tumor-targeting moiety (TTM) and a cytotoxic drug connected through a suitable linker system. These TTDDSs exploit the unique and intrinsic properties of cancer cells to selectively deliver cytotoxic agents to the tumor. An ideal linker system must remain stable during blood circulation, but be readily cleaved to release the active agent upon internalization or accumulation in the tumor microenvironment.
The problem is to find a TDDD that is capable of selectively delivering a cytotoxic agent that effectively kills tumor cells. The present disclosure describes such a TDDD.